The objective of this proposal is to determine if Trifluorosal, a new proprietary anti-inflammatory drug possessing other beneficial properties, can prevent the formation of UV induced papillomas and carcinomas in exposed mouse skin when applied topically. Trifluorosal belongs to a class of patented antibacterial/anti-inflammatory agents, the 5-(n-alkylsulfonyl) salicylanilides. We have recently found that a topical application of Trifluorosal can enhance DNA repair in mouse skin exposed to UV radiation, and that Trifluorosal can inhibit the growth of human tumor cells in-vitro. Some of these effects may be due to Trifluorosal's ability to inhibit enzymes in the prostaglandin synthetase pathway. Trifluorosal's physicochemical properties, including its high lipophilicity, low systemic absorption, lack of toxicity and excellent substantivity make this compound well suited for topical use. The specific goals of this proposal are directed toward proving the feasibility of developing a topical pharmaceutical formulation containing Trifluorosal as a treatment for the effects of UV radiation on skin, and to determine Trifluorosal's mechanism of action. In Phase II we intend to develop an optimized topical pharmaceutical formulation containing Trifluorosal and complete additional safety and efficacy studies of the optimized formulation to support the filing of an IND application with the FDA to commence clinical studies. PROPOSED COMMERCIAL APPLICATIONS: The National Cancer Institute estimates that 50 percent of Americans who live to the age of 65 will have at least one episode of skin cancer. The risk of developing malignant melanoma during a lifetime has increased from 1 in 1,200 during 1935 to 1 in 87 during 1999. The sales of sun preparations products in mass retail outlets exceeded $500 million in 1998, growing almost 10% from the previous year. Clearly there is a desire for more effective products to prevent or reverse the adverse effects of sunlight exposure.